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Randomized peptide assemblies for enhancing immune responses to nanomaterials.

Nicole L Votaw1, Lauren Collier1, Elizabeth J Curvino1

  • 1Department of Biomedical Engineering, Duke University, Durham, NC, 27708, United States.

Biomaterials
|April 26, 2021
PubMed
Summary

Researchers developed novel polypeptide nanomaterials that induce strong immune responses with minimal inflammation. These biomaterials show promise for vaccine development and tissue repair applications.

Keywords:
EpitopeGlatiramer acetateNanofiberSelf-assemblingSupramolecularVaccine

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Area of Science:

  • Biomaterials Science
  • Immunology
  • Nanotechnology

Background:

  • Biomaterials that modulate immune responses without causing significant inflammation are crucial for applications like tissue repair and vaccines.
  • Glatiramoids, a class of immunomodulatory random copolymers, inspired the design of new biomaterials.

Purpose of the Study:

  • To design and synthesize self-assembling randomized polypeptide nanomaterials.
  • To investigate if these nanomaterials could elicit Type 2 immunity and T helper 2 (TH2) T-cell responses.
  • To evaluate their potential to enhance immune responses to co-assembled epitopes without adjuvants.

Main Methods:

  • Developed a method for synthesizing self-assembling peptides with randomized polypeptide libraries (KEYA).
  • Characterized the formation of regular nanofibers.
  • Assessed antigen-presenting cell uptake in vitro.
  • Evaluated immune responses, including antibody production, T-cell responses, and cytokine profiles (IL-4) in vivo.
  • Measured footpad swelling to assess inflammation.

Main Results:

  • Synthesized KEYA-modified peptides that self-assembled into regular nanofibers with good reproducibility.
  • KEYA modifications significantly enhanced antigen-presenting cell uptake and induced strong antibody responses without adjuvants.
  • KEYA nanofibers acted as potent B-cell and T-cell epitopes, boosting responses to relevant antigens (influenza, chronic inflammation) and inducing a Type 2/TH2/IL-4 phenotype.
  • Increased IL-4 production by T cells, prolonged nanofiber residence time, and minimal inflammation (no swelling) were observed.
  • Decreased overall T-cell expansion suggested a TH2-skewed response.

Conclusions:

  • Introduced a novel biomaterial (KEYA-modified polypeptide nanofibers) capable of inducing robust Type 2/TH2/IL-4 immune responses.
  • Demonstrated the potential of these nanomaterials to act as effective vaccine adjuvants or components.
  • Highlighted their utility in applications requiring controlled immune stimulation with reduced inflammation, such as vaccination and tissue regeneration.